Subcutaneous interleukin-2 and interferon α in the treatment of patients with metastatic renal cell carcinoma—Less efficacy compared with intravenous interleukin-2 and interferon α

Results of a multicenter Phase II trial from the Groupe Français d'Immunothérapie


  • In addition to the authors cited, the following investigators and centers also participated in the trial: Stéphane Culine (Centre Val d'Aurelle, Montpellier); Antoine Thyss and Jean-Marc Ferrero (Centre André Lacassagne, Nice); Hervé; Cure and Joël Fleury (Centre Jean Perrin, Clermont-Ferrand); Laurent Mignot (Hopital Foch, Suresnes); Patrice Viens (Institut Paoli Calmettes, Marseille); Alain Goupil (Centre René Huguenin, Saint-Cloud); Jean-Claude Barats (Centre Hospitalier, Colmar); Eric Legouffe and Jean-François Rossi (Centre Hospitalier Universitaire, Montpellier); and Isabelle Calmés and Michel Drevon at the Data Monitoring and Statistical Center (Centre Léon Bérard, Lyon).



The main objective of this trial was to evaluate the combination of subcutaneous (SC) interleukin-2 (IL-2) with interferon α-2a (IFN-α) in the treatment of patients with metastatic renal cell carcinoma (MRCC) compared with a previous trial that used continuous-infusion IL-2 and IFN-α with identical schedules and dosages.


Between April, 1997 and January, 1998, 66 patients with MRCC received SC IL-2 at a dose of 9 × 106 IU/m2 twice daily for 5 days during 2 induction cycles and during 4 additional cycles, with a 3-week rest between cycles. Each induction cycle consisted of two 5-day courses of IL-2 separated by a 9-day break. IFN-α at a dose of 6 × 106 IU per day three times per week was given during induction cycles and additional cycles.


All patients were assessable for response and toxicity. The median follow-up was 43 months. Thirty-five patients (51%) and 43 patients (63%) received ≥ 80% of the planned induction doses of IL-2 and IFN-α, respectively. Five patients achieved objective responses (7.6%; 95% confidence interval [95%CI], 2.5–16.8%), with two complete responses. The median survival was 14 months (95%CI, 11.3–16.7 months). Fifty-three patients (80%) had at least one episode of Grade 3 toxicity related to treatment. Twenty-two patients developed Grade 4 toxicities, which included hypotension (24% of patients), decreased performance status (6% of patients), dyspnea (3% of patients), and mucositis (3% patients) as well as fever, ventricular tachycardia, and anemia.


The current results seem to indicate reduced efficacy and higher toxicity rates with SC IL-2 plus IFN-α compared with the results from a previous trial that used an identical regimen with IV IL-2 administration. Although SC IL-2 regimens are used widely, their interest remains to be determined. Cancer 2002;95:2324–30. © 2002 American Cancer Society.

DOI 10.1002/cncr.10968